The longterm objective of the proposed studies remains to elucidate fully the biologic mechanisms by which IgE antibody induces acute allergic reactions. We continue to use the rabbit model we developed several years ago in which rabbits are immunized initially as neonates so as to induce preferentially antibodies of the IgE class. Purified rabbit IgE will also be used to provide passively sensitized animals. It is our plan to establish firmly that IgE is the necessary and sufficient trigger of the allergic reactions resulting from antigen challenge. We will continue our characterization of the levels of participation of the various cells and mediators in the IgE-induced respiratory and circulatory responses and how that participation varies in different forms of the allergic response (systemic anaphylaxis following intravenous antigen challenge and the early and late phase reactions following aerosol antigen challenge). In the anaphylactic reactions, we will attempt to define precisely the roles of leukotrienes, platelet activating factor and the neuropeptides released from capsaicin-sensitive afferent neurons. These and other mediators (histamine and prostaglandins) will be studied in relation to the responses to aerosol antigen challenge. The capacity of anesthetics to suppress the late phase response to aerosol antigen challenge will be documented. The role of the neutrophil will be determined in each form of the allergic response. Finally the influence of specific IgG (given in varying concentrations) will be determined.